Flavonols in Action: Targeting Oxidative Stress and Neuroinflammation in Major Depressive Disorder

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(8), С. 6888 - 6888

Опубликована: Апрель 7, 2023

Major depressive disorder is one of the most common mental illnesses that highly impairs quality life. Pharmacological interventions are mainly focused on altered monoamine neurotransmission, which considered primary event underlying disease's etiology. However, many other neuropathological mechanisms contribute to progression and clinical symptoms have been identified. These include oxidative stress, neuroinflammation, hippocampal atrophy, reduced synaptic plasticity neurogenesis, depletion neurotrophic factors, dysfunction hypothalamic-pituitary-adrenal (HPA) axis. Current therapeutic options often unsatisfactory associated with adverse effects. This review highlights relevant findings concerning role flavonols, a ubiquitous class flavonoids in human diet, as potential antidepressant agents. In general, flavonols be both an effective safe option management depression, largely based their prominent antioxidative anti-inflammatory Moreover, preclinical studies provided evidence they capable restoring neuroendocrine control HPA axis, promoting alleviating depressive-like behavior. Although these promising, still far from being implemented practice. Hence, further needed more comprehensively evaluate respect improvement signs depression.

Язык: Английский

---

Cerebellar nuclei neurons projecting to the lateral parabrachial nucleus modulate classical fear conditioning

Cell Reports, Год журнала: 2023, Номер 42(4), С. 112291 - 112291

Опубликована: Март 22, 2023

Multiple brain regions are engaged in classical fear conditioning. Despite evidence for cerebellar involvement conditioning, the mechanisms by which outputs modulate learning and memory remain unclear. We identify a population of deep nucleus (DCN) neurons with monosynaptic glutamatergic projections to lateral parabrachial (lPBN) (DCN→lPBN neurons) mice. While optogenetic suppression DCN→lPBN impairs auditory memory, activation elicits freezing behavior only after Moreover, conditioning potentiates DCN-lPBN synapses, subsequently, cue activates lPBN Furthermore, neuron can replace but not footshock These findings demonstrate that nuclei via transmitting conditioned stimuli signals lPBN. Collectively, our suggest circuit is part neuronal substrates within interconnected underscoring memory.

Язык: Английский

---

Variations on the theme: focus on cerebellum and emotional processing

Frontiers in Systems Neuroscience, Год журнала: 2023, Номер 17

Опубликована: Май 10, 2023

The cerebellum operates exploiting a complex modular organization and unified computational algorithm adapted to different behavioral contexts. Recent observations suggest that the is involved not just in motor but also emotional cognitive processing. It therefore critical identify specific regional connectivity microcircuit properties of cerebellum. studies are highlighting differential localization genes, molecules, synaptic mechanisms wiring. However, impact these differences fully understood will require experimental investigation modeling. This review focuses on cellular circuit underpinnings cerebellar role emotion. And since emotion involves an integration cognitive, somatomotor, autonomic activity, we elaborate tradeoff between segregation distribution three main functions

Язык: Английский

---

Human cerebellum and ventral tegmental area interact during extinction of learned fear

Опубликована: Янв. 31, 2025

The key elements for fear extinction learning are unexpected omissions of expected aversive events, which considered to be rewarding. Given its reception reward information, we tested the hypothesis that cerebellum contributes prediction error processing driving via connections with ventral tegmental area (VTA). Forty-three young and healthy participants performed a three-day conditioning paradigm in 7T MR scanner. VTA were active during unconditioned stimuli, particularly initial trials. Increased functional connectivity was observed between VTA, indicating could positively modulate activity, turn might facilitate dopaminergic signaling learning. These results imply an interaction should incorporated into existing model network.

Язык: Английский

---

Recent Advances in the Understanding of Specific Efferent Pathways Emerging From the Cerebellum

Frontiers in Neuroanatomy, Год журнала: 2021, Номер 15

Опубликована: Дек. 16, 2021

The cerebellum has a long history in terms of research on its network structures and motor functions, yet our understanding them further advanced recent years owing to technical developments, such as viral tracers, optogenetic chemogenetic manipulation, single cell gene expression analyses. Specifically, it is now widely accepted that the also involved non-motor cognitive psychological mainly from studies have clarified neuronal pathways other brain regions are relevant these functions. techniques manipulate specific were effectively utilized demonstrate involvement without altering activity. In particular, cerebellar efferent recently gained attention not only monosynaptic connections regions, including periaqueductal gray ventral tegmental area, but polysynaptic non-primary cortex hippocampus. Besides associated with using sophisticated experimental characterized historically studied primarily Nevertheless, knowledge, there no articles comprehensively describe various pathways, although many interesting review focusing functions or pathways. Here, we summarize findings networks projecting several regions. We introduce enabled us advance discuss possible directions for future regarding their

Язык: Английский

---

Cerebellum and hippocampus abnormalities in patients with insomnia comorbid depression: a study on cerebral blood perfusion and functional connectivity

Frontiers in Neuroscience, Год журнала: 2023, Номер 17

Опубликована: Июнь 16, 2023

Chronic insomnia disorder and major depressive are highly-occurred mental diseases with extensive social harm. The comorbidity of these two is commonly seen in clinical practice, but the mechanism remains unclear. To observe characteristics cerebral blood perfusion functional connectivity patients, so as to explore potential pathogenesis biological imaging markers, thereby improving understanding their mechanism. 44 patients chronic comorbid 43 healthy controls were recruited this study. severity depression assessed by questionnaire. values participants obtained to, analyze correlation questionnaire scores. flow cerebellum, vermis, right hippocampus, left parahippocampal gyrus reduced, which was negatively related or depression. connectivities cerebellum-right putamen hippocampus-left inferior frontal increased, showing positive correlations Decreased cerebellum-left fusiform gyrus, occipital lobe, hippocampus-right paracentral lobule, precentral partially associated may mediate between Insomnia can cause changes brain function. Changes cerebellar hippocampal regions result They reflect abnormalities sleep emotion regulation. That be involved comorbidity.

Язык: Английский

---

Cerebellar Circuits for Classical Fear Conditioning

Frontiers in Cellular Neuroscience, Год журнала: 2022, Номер 16

Опубликована: Март 30, 2022

Accumulating evidence indicates that the cerebellum is critically involved in modulating non-motor behaviors, including cognition and emotional processing. Both imaging lesion studies strongly suggest a component of fear memory network. Given well-established role adaptive prediction movement cognition, likely to be engaged learned threats. The activated by learning, learning induces changes at multiple synaptic sites cerebellum. Furthermore, recent technological advances have enabled investigation causal relationships between intra- extra-cerebellar circuits fear-related behaviors such as freezing. Here, we review literature on mechanisms underlying modulation cerebellar mammalian brain conditioning cellular levels elucidate contributions distinct structures memory. This knowledge may facilitate deeper understanding development more effective treatment strategies for affective disorders post-traumatic stress or anxiety related disorders.

Язык: Английский

---

Lateral hypothalamus orexinergic projection to the medial prefrontal cortex modulates chronic stress-induced anhedonia but not anxiety and despair

Translational Psychiatry, Год журнала: 2024, Номер 14(1)

Опубликована: Март 16, 2024

Abstract Chronic stress-induced anxiodepression is a common health problem, however its potential neurocircuitry mechanism remains unclear. We used behavioral, patch-clamp electrophysiology, chemogenetic, and optogenetic approaches to clarify the response of lateral hypothalamus (LH) medial prefrontal cortex (mPFC) stress, confirmed structural connections between LH mPFC, investigated role LH–mPFC pathway in chronic symptoms. Unpredictable mild stress (UCMS) caused anxiodepression-like behaviors, including anxiety, anhedonia, despair behaviors. discovered that activity mPFC was both increased after restraint (RS), stressor UCMS. Then we found orexinergic neurons predominantly project glutamatergic excitability these were In addition, overactivated terminals induced anhedonia but not anxiety behaviors naive mice. Moreover, chemogenetically inhibited projection blocked orexin receptors alleviated UCMS-treated Our study identified new neurocircuit from revealed regulating stress.

Язык: Английский

---

Blocking IL-17A prevents oxycodone-induced depression-like effects and elevation of IL-6 levels in the ventral tegmental area and reduces oxycodone-derived physical dependence in rats

Brain Behavior and Immunity, Год журнала: 2024, Номер 117, С. 100 - 111

Опубликована: Янв. 8, 2024

Язык: Английский

---

Immune-Triggered Forms of Plasticity Across Brain Regions

Frontiers in Cellular Neuroscience, Год журнала: 2022, Номер 16

Опубликована: Июль 22, 2022

Immune cells play numerous roles in the host defense against invasion of microorganisms and pathogens, which induces release inflammatory mediators (e.g., cytokines chemokines). In CNS, microglia is major resident immune cell. Recent efforts have revealed diversity cell types heterogeneity their functions. The refinement synapse structure was a hallmark feature microglia, while they are also involved myelination capillary dynamics. Another promising modulation synaptic transmission as plasticity intrinsic excitability neurons non-synaptic plasticity. Those modulations physiological properties considered induced by both transient chronic exposures to mediators, cause behavioral disorders seen mental illness. It plausible for astrocytes pericytes other than macrophage induce immune-triggered neurons. However, current understanding has yet achieved unveil what from or glia form modulating pre-, post-synaptic functions still unclear ion channels intracellular signaling brain regions CNS involved. this review, we introduce ubiquitous efficacy across related with mechanism induction. Specifically, compare neuro-modulation mechanisms cerebellar Purkinje cerebral pyramidal neurons, stressing inverted directionality We discuss suppression augmentation extent meta-plasticity immunity. Lastly, sum up forms different disease relevance. Together, immunity influences our cognition, sense, memory, behavior

Язык: Английский

---